Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

2504 - Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic Large Cell Neuroendocrine Carcinoma (LCNEC)

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Translational Research

Tumour Site

Neuroendocrine Tumours

Presenters

Bregtje Hermans

Citation

Annals of Oncology (2018) 29 (suppl_8): viii641-viii644. 10.1093/annonc/mdy301

Authors

B.C.M. Hermans1, J.L. Derks1, E. Thunissen2, R.J. van Suylen3, M.A. den Bakker4, H.J.M. Groen5, E.F. Smit6, R.A. Damhuis7, E.C. van den Broek8, P. PALGA-group8, C.M. Stallinga9, G.M. Roemen9, E.J. Speel9, A.C. Dingemans1

Author affiliations

  • 1 Pulmonary Diseases, Maastricht University Medical Center (MUMC), P.O. Box 616 - Maastricht/NL
  • 2 Pathology, VU medical centre, Amsterdam/NL
  • 3 Pathology-dna, Jeroen Bosch Ziekenhuis, Den Bosch/NL
  • 4 Pathology, Erasmus University Medical Center, 3015 CE - Rotterdam/NL
  • 5 Pulmonary Disease, University Hospital Groningen (UMCG), 9700 RB - Groningen/NL
  • 6 Thoracic Oncology, Netherlands Cancer Institute, Amsterdam/NL
  • 7 Research, Comprehensive Cancer Association, Utrecht/NL
  • 8 Palga, PALGA foundation, Houten/NL
  • 9 Pathology, Maastricht University Medical Center, Maastricht/NL
More

Resources

Abstract 2504

Background

Pulmonary LCNEC is a rare tumor. Two mutually exclusive subtypes of LCNEC are recognized, the co-mutated TP53 and RB1 and the STK11/KEAP1 (predominantly RB1 wildtype) group. We investigated PD-L1 expression in a well characterized stage IV LCNEC cohort and compared expression in the two subtypes.

Methods

Panel-consensus pathology revision was performed along with targeted next generation sequencing (TNGS) for genes TP53, RB1, STK11 and KEAP1 and immunohistochemical (IHC) analysis of RB1, on pretreatment tumor samples of stage IV LCNEC treated with chemotherapy (Derks et al. CCR 2018). IHC staining for PD-L1 (DAKO 28-8) was performed according to standard protocols on the DAKO autostainer and evaluated by an experienced screener. Tumors were scored positive if > 1% of tumor cells showed any membranous staining. Overall survival (OS) was evaluated by Kaplan Meier analysis and differences estimated with Log-Rank test. Cox-regression analysis included PD-L1, age and gender.

Results

PD-L1 IHC expression data could be generated in 98/147 confirmed LCNEC samples along with RB1 IHC (n = 97) of which 77 passed quality control for TNGS. PD-L1 expression was positive in 16/98 cases (16%); n = 5 (5%) with >50%, n = 11 (11%) having >1-50% and n = 82 (82%) with ≤1% membranous staining, respectively. No significant correlation of PD-L1 expression with molecular subtyping of LCNEC was identified (Table). PD-L1 expression was correlated with a superior OS, hazard ratio (HR) 0.54 ((95% Confidence interval (CI), 0.31-0.96) P = 0.034.Table: 1813P

Expression of PD-L1 in LCNEC, correlated to molecular data

PD-L1 +PD-L1 -P-value
LCNEC (n = 98)16%84%-
1-5%7 %--
5-204%--
>505%--
Rb1 IHC (n = 97)
RB1 (+) (n = 29)10%90%NS
RB1 (-) (n = 68)19%81%
Mutation status (n = 76)
RB1/TP53 mutated (n = 33)15%85%NS
RB1 wildtype (n = 43)16%84%
OS in months (95% CI)8.9 (4.2-13.6)6.6 (5.7-7.6)HR 0.54 (0.31-0.96) P = 0.034

Conclusions

PD-L1 expression was positive in 16% of stage IV LCNEC tumors. PD-L1 expression is an independent process from LCNEC molecular subgroups. In LCNEC patients with PD-L1 expression superior OS is observed compared to those with negative PD-L1 tumors.

Clinical trial identification

Legal entity responsible for the study

Maastricht University Medical Centre, Department of Pulmonary Disease.

Funding

Bristol-Meyers Squibb.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.